There is evidence about the importance of sex in pain. The purpose of this study was to investigate the effect of sex in the antiallodynic activity of spinal dopamine D-and D-like receptors in a model of fibromyalgia-type pain in rats. Reserpine induced the same extent of tactile allodynia in female and male rats. Intrathecal injection of SCH- 23390 (3-30 nmol, D-like receptor antagonist), pramipexole (0.15-15 nmol) or quinpirole (1-10 nmol D-like receptor agonists) increased withdrawal threshold in reserpine-treated female rats. Those drugs induced a greater antiallodynic effect in female rats. Sex-difference was also observed in a nerve injury model. Ovariectomy abated the antiallodynic effect of SCH- 23390 (30 nmol) in reserpine-treated rats, while systemic reconstitution of 17β-estradiol levels or intrathecal injection estrogen receptor-α agonist protopanaxatriol in ovariectomized reserpine-treated females restored the antiallodynic effect of SCH- 23390. Intrathecal administration of ICI-182,780 (estrogen receptor-α/β antagonist) or methyl-piperidino-pyrazole hydrate (estrogen receptor-α antagonist) abated 17β-estradiol-restored antiallodynic effect of SCH- 23390 in rats. In contrast, ovariectomy slightly reduced the effect of pramipexole (15 nmol) or quinpirole (10 nmol) in reserpine-treated rats, whereas systemic reconstitution of 17β-estradiol levels did not modify the antiallodynic effect of both drugs. Combination 17β-estradiol/progesterone, but not 17β-estradiol nor progesterone alone, restored the antiallodynic effect of pramipexole and quinpirole in the rats. Mifepristone (progesterone receptor antagonist) abated 17β-estradiol + progesterone restoration of antiallodynic effect of pramipexole and quinpirole. These data suggest that the antiallodynic effect of dopamine D-and D-like receptors in fibromyalgia-type pain depends on spinal 17β-estradiol/estrogen receptor-α and progesterone receptors, respectively.
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